The objective of work supported by this grant is to determine the role of endogenous (germ line transmitted) MuMTV genes in neoplastic transformation of normal mammary cells under impress of mammotropic hormonal stimulations in vitro. We have established that a major locus of controls over MuMTV gene expression in both normal and malignant Balb/c mammary cells is post-transcriptional. We propose to determine how hormones that promote transformation of mammary cells effect those controls. We have isolated tumorigenic clones from mammary tumors and non-tumorigenic clones from mammary glands in a specially devised suspension culture system. We propose to transform the non-tumorigenic cells and determine concordant pertubations in MuMTV gene expression. We propose to define the tumorigenic phenotype in terms of altered proliferative responses to mammotropic hormones using these cells in the suspension culture system.